Evaluation of a panel of human monoclonal antibodies to D and exploration of the synergistic effects of blending IgG1 and IgG3 antibodies on their invitro biologic function

BACKGROUND: The D immunoprophylaxis program has successfully reduced the in cidence of Rh hemolytic disease of the newborn (HDN), but it has also reduc ed the availability of plasma-derived polyclonal anti-D, which constitutes the current therapeutic product. Human monoclonal anti-D from hybridoma cel l lines may be an acceptable alternative, and clinical efficacy of each ant i-D is being evaluated in several centers. STUDY DESIGN AND METHODS: This study represents the largest assessment (out side of the international Workshops) of human D monoclonal antibodies for p otential therapeutic use. The in vitro biologic activity and immunologic an d serologic reactivity of a coded panel of 20 D antibodies (THERAD) was inv estigated. The bioassays used were lymphocyte (K-cell) antibody-dependent c ell-mediated cytotoxicity (ADCC), monocyte ADCC, and monocyte chemiluminesc ence, which together reflect the processes involved in antibody-coated red cell destruction in vivo. From this panel, six antibodies (THERADs 14, 19, 22, 23, 27, and 28, comprising 3 IgG1 and 3 IgG3 D monoclonal antibodies) w ere further selected to investigate the effects of blending in the three bi oassays. RESULTS: Several THERAD blends displayed greater activity than their compon ent parts, in the range of 6 to 124 percent. There was no evidence to sugge st functional blocking effects with this restricted panel of antibodies. CONCLUSION: The THERAD blends containing both IgG1 and IgG3 anti-D appeared to be the most functionally active, as did blends containing antibodies to two distinct D epitopes. This in vitro evidence has important implications for the future formulation of an effective monoclonal preparation for the prevention of Rh HDN.